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Development of a lipopolysaccharide-targeted peptide mimic vaccine against Q fever.

ABSTRACT: Coxiella burnetii is a Gram-negative bacterium that causes acute and chronic Q fever in humans. Creation of a safe and effective new generation vaccine to prevent Q fever remains an important public health goal. Previous studies suggested that Ab-mediated immunity to C. burnetii phase I LPS (PI-LPS) is protective. To identify the potential peptides that can mimic the protective epitopes on PI-LPS, a PI-LPS-specific mAb 1E4 was generated, characterized, and used to screen a phage display library. Interestingly, our results indicate that 1E4 was able to inhibit C. burnetii infection in vivo, suggesting that 1E4 is a protective mAb. After three rounds of biopanning by 1E4 from the phage display library, a mimetic peptide, m1E41920, was identified, chemically synthesized, and conjugated to keyhole limpet hemocyanin (KLH) for examining its immunogenicity. The results indicate that the synthetic peptide m1E41920 was able to inhibit the binding of 1E4 to PI Ag, suggesting m1E41920 shares the same binding site of 1E4 with the epitopes of PI Ag. In addition, m1E41920-KLH elicited a specific IgG response to PI Ag, and immune sera from m1E41920-KLH-immunized mice was able to inhibit C. burnetii infection in vivo, suggesting that m1E41920 may specifically mimic the protective epitope of PI-LPS. Furthermore, m1E41920-KLH was able to confer significant protection against C. burnetii challenge. Thus, m1E41920-KLH is a protective Ag and may be useful for developing a safe and effective vaccine against Q fever. This study demonstrates the feasibility of developing a peptide mimic vaccine against Q fever.

SUBMITTER: Peng Y

PROVIDER: S-EPMC3833726 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Development of a lipopolysaccharide-targeted peptide mimic vaccine against Q fever.

Peng Ying Y Zhang Yan Y Mitchell William J WJ Zhang Guoquan G

Journal of immunology (Baltimore, Md. : 1950) 20121010 10

Coxiella burnetii is a Gram-negative bacterium that causes acute and chronic Q fever in humans. Creation of a safe and effective new generation vaccine to prevent Q fever remains an important public health goal. Previous studies suggested that Ab-mediated immunity to C. burnetii phase I LPS (PI-LPS) is protective. To identify the potential peptides that can mimic the protective epitopes on PI-LPS, a PI-LPS-specific mAb 1E4 was generated, characterized, and used to screen a phage display library. ...[more]

PMID: 23053512

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Project description:Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.

Dataset Information

Development of a lipopolysaccharide-targeted peptide mimic vaccine against Q fever.

Publications

Development of a lipopolysaccharide-targeted peptide mimic vaccine against Q fever.

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